Bis-(2-pyridyl-1-oxide) disulfide

ABSTRACT

An improved integrated route to bis-(2-pyridyl-1-oxide) disulfide is provided by oxidizing 2-chloropyridine with permaleic acid to form 2-chloropyridine-1-oxide followed by mercaptization with a selected alkali metal sulfide to form the alkali metal salt of 2-mercaptopyridine-1-oxide and then oxidation with hydrogen peroxide under selected pH conditions.

United States Patent Hooks, Jr. et al.

BIS-(Z-PYRIDYL-l-OXIDE) DISULFIDE Inventors: Haywood Hooks, Jr., WestHaven;

James J. Pitts, Hamden, both of Conn.

Olin Corporation, New Haven,

Conn.

Filed: May 2, 1974 Appl. No.: 466,328

Assignee:

U.S. Cl. ..260/294.8 J; 260/290 HL; 260/294.8 G Int. Cl. C07D 211/70Field of Search. 260/294.8 J, 290 l-lL, 294.8 G

References Cited UNITED STATES PATENTS 8/1954 Shaw et a1. 260/294.8 G

[ July 1,1975

2,742,476 4/1956 Bernstein et a]. 260/2943 .1 2,951,844 9/1960 Sherme'r260/290 HL 3,759,932 9/]973 Gavin et a]. 260/2948 G PrimaryExaminer-Alan L. Rotman Attorney, Agent, or Firm-Robert L. Andersen 5 7]ABSTRACT to bis-(2-pyridyl-lby oxidizing 2- 8 Claims, No DrawingsBIS-(Z-PYRIDY-L-l-OXIDE) DISULFIDE wherein mercaptopyridine-l-oxide isreacted with an oxidizing'agent. U.S. Pat. No. 3,759,932 also generallydiscloses the preparation of a disulfide compound using an in.-situpreparation technique wherein? mercaptopyridine is not "isolated.-rWh-ile these references broadly disclose the preparati'on' of thedisulfide, problems have arisen when using the alkali metal salt ofZ-mercaptopyridine-l-oxide in an in-situ technique wherein the alkalimetal salt was obtained by oxidizing 2-chloropyridine with permaleicacid ,to form the N- oxide followed by mercaptization to form the salt.When using this system, oxidationby the; known techniques as shownfor,example in U.S. Pat. No. 2,742,476 resulted in the formation ofundesired by-products such as the alkali metal maleate and alkali-metalfumarate. This contaminated the desired disulfideproduct and lowered theyield. K

lthas now been found that-when using permaleic acid in the preparationof 2-chloropyridine-l-oxide during the integrated preparation of thedisulfide, the above noted by-product formation can be avoided andsurprisingly high yields obtained by operating the final oxidation inthe presence of hydrogen peroxide at selected 1 pH conditions. Moreparticularly the oxidation .of the alkali metal salt of 'zrriercaptopyridine-l-oxide is carried out at a pH of about 4 to about 5 andpreferably from about 4.5 to about 5. The overall reaction scheme ofthis invention is illustrated by the following equation:

drosulfide in accordance with known procedures as disclosed if] Us; Pat.No. 2,686,786.1"he'key step in this invention is the oxidation ofjthepreparedlalkali metal salt of2-mercaptopyridinel' oxide using hydrogenperoxide and a reaction pH of about i to about 5. By main? taining. thereaction under these conditions, the'precipitation of unde's i're'dimpurities, primarily derived from the salts of fumaricacid is avoidedand surprisingly high yields resulted. a g 3' In carrying outthereactionof this inventior -the temperature may generally bemaintained fromabout 15 to about 35C. with about 20 to about 30C beingpreferred. The hydrogen peroxide concentration may be varied with about5 to about 30 percent in aqueous solution being generally used.Generally a stoichiometi' ric. ratio of the alkali metal salt of2-mercaptopyridine and hydrogen peroxide of about 2 moles of themercaptopyri dine salt to about 1 mole of peroxide or a slight excess ofup to about 15 percent peroxide is used.

It is alsojgenerally advisable to agitate the reaction mixture in theperoxide oxidation step to maintain an effectively dilute hydrogenperoxide solution. 1

The pH of the reaction mixture is generally adjusted before the peroxideoxidation step by using any suitable acidifying agent such as thenon-oxidizing mineral acids such as HCl andthe non-oxidizing organicacids.

While '2-chloropyridine has been shown to be a desired starting materialin the method {of this invention. other -2-halopyridine's* andsubstituted halopy ridines containing groups such as lower alkyl andlower alkoxy which do not adversely affect the reaction may also beused.

Isolation of the final product after oxidation is obtained by a standardfiltration procedure.

The 'disulf ed compounds prepared in accordance with the method of thisinvention have a variety of known uses, particularly as antibacterialandantifungal agentsin a variety of applications such as to combatagricultural plant diseases, and in plastics and fabrics to resistmildew or other fungus attack as disclosedin U.S. Pat. No. 2,742,476.

The following examples are further illustrative of this invention.

EXAMPLE I A 2-liter, 3-neck flask fitted with a stirrer, thermometer andaddition funnel was charged with 1,866 g of a reaction mixturecontaining the sodium salt of 2-mercaptopyridine-l-oxide. This reactionmixture had an assay of 7.2 percent 135 g) of the sodium salt of2-mercaptopyridine-l-oxide, 7 percent sodium chloride and 13-14 percenttotal of sodium maleate and sodium fumarate. This mixture was obtainedby oxidizing 2-chloropyridine with permaleic acid and then mercaptizingwith NaSH. The pH was then adjusted to 4.5 with concentratedhydrochloric acid and the resulting warm solution was cooled to 25C. and52 ml. of30 percent hydrogen peroxide 12 percent excess overstoichiometry) in l60 ml. water added dropwise over a 30 minute periodwith stirring. The reaction was slightly exothermic with the temperaturerising to approximately 30C. at the end of the peroxide addition.Stirring of the now precipitated bis-(2-pyridyl-l-oxide) disulfideproduct was continued for 2 more hours to assure completeness of thereaction. The disulfide product formed was collected by filtration andthe filter cake washed with 50 ml. water follower by 50 ml of methanol.After air drying, a total of 1 12 g (98 percent yield based on startingsodium salt of 2-mercaptopyridine-l-oxide) of bis-(Z-pyridyl-l-oxide)disulfide was obtained with a melting point of 20020lC. and an assay of98 percent.

EXAMPLE ll Using the same procedure as Example I with a reaction mixturecontaining 25.6 g of the sodium salt of Z-mercaptopyridine-l-oxide, 14 gof percent hydrogen peroxide, a pH of 4.0 and a reaction time of 18hours, 17.0 g of the disulfide product was obtained (79.8 percent yieldbased on sodium salt) having as assay of 97.8 percent.

EXAMPLE lll Using the same procedure Example I with a reaction mixturecontaining 25.6 g of the sodium salt of 2-mercaptopyridine-l-oxide, 14 gof 10 percent hydrogen peroxide, a pH of 5.0, a reaction temperature of20 to 23C. and a reaction time of 18 hours, 19.0 g of the disulfideproduct was obtained (89.3 percent yield based on sodium salt) and anassay of 97.7 percent.

EXAMPLE [V For comparative purposes, the same procedure as Example IIwas followed with a pH of 3.0. A product of 23.5 g was obtained,however, it was contaminated with significant quantities of furmaricacid impurities.

EXAMPLE V For, comparative purposes, the same procuedure as Example IIIwas followed with a pH of 5.5 and a reaction time of 72 hours. A productof 10.5 g (49.3 percent yield) was obtained.

What is claimed is:

1. In the method of preparing bis-(Z-pyridyll -oxide) disulfide wherein2-chloropyridine is oxidized with permaleic acid to form a reactionmixture containing 2- chloropyridine-l-oxide which is mercaptizedusingan alkali metal sulfide or alkali metal hydrosulfide to form thealkali metal salt of.Z-mercaptopyridine-l-oxide in solution, theimprovement comprising adjusting the pH of the resulting solution to apH of about 4 to about 5 and then oxidizing with hydrogen peroxide toform the bis-(Z-pyridyl-l-oxide) disulfide compound.

2. The method of claim 1 wherein said alkali metal is sodium.

3. The method of claim 2 wherein a pH of about 4.5 to about 5 is used.

4. The method of claim 2 wherein said hydrogen peroxide oxidation iscarried out at a temperature of from about 15 to about 35C.

5. The method of claim 4 wherein a hydrogen peroxide concentration offrom about 5 to about 30 percent in aqueous solution is used.

6. The method of claim 5 wherein said resulting solution contains sodiumfumarate and sodium maleate in addition to the sodium 'salt of2-mercaptopyridine-loxide.

7. The method of claim 5 wherein a pH of about 4.5 to about 5 is used.

8. The method of claim 7 wherein a temperature of from about 20 to about30C. is used.

1. IN THE METHOD OF PREPARING BIS-(2PYRIDYL-1-OXIDE) DISULFIDE WHEREIN2-CHLOROPYRIDINE IS OXIDIZED WITH PERMALEIC ACID TO FORM A REACTIONMIXTURE CONTAINING 2-CHLOROPYRIDINE-1OXIDE WHICH IS MERCAPTIZED USING ANALKALI METAL SULFIDE OR ALKALI METAL HYDROSULFIDE TO FORM THE ALKALIMETAL SALT OF 2MERCAPTOPYRIDINE-1-OXIDE IN SOLUTION, THE IMPROVEMENTCOMPRISING ADJUSTING THE PH OF THE RESULTING SOLUTION TO A PH OF ABOUT 4TO ABOUT 5 AND THEN OXIDIZING WITH HYDROGEN PEROXIDE TO FORM THEBIS-(2PYRIDYL-1-OXIDE) DISULFIDE COMPOUND.
 2. The method of claim 1wherein said alkali metal is sodium.
 3. The method of claim 2 wherein apH of about 4.5 to about 5 is used.
 4. The method of claim 2 whereinsaid hydrogen peroxide oxidation is carried out at a temperature of fromabout 15* to about 35*C.
 5. The method of claim 4 wherein a hydrogenperoxide concentration of from about 5 to about 30 percent in aqueoussolution is used.
 6. The method of claim 5 wherein said resultingsolution contains sodium fumarate and sodium maleate in addition to thesodium salt of 2-mercaptopyridine-1-oxide.
 7. The method of claim 5wherein a pH of about 4.5 to about 5 is used.
 8. The method of claim 7wherein a temperature of from about 20* to about 30*C. is used.